Pharmacological modulation of 2-AG signaling pathway
In a subset of experiments focused on the MPP – DG synapse from control and MK-801-treated slices, WIN 55,212-2, a CB1R agonist (WIN, 5 µM), was bath perfused for 15 minutes to examine the presynaptic induction of LTD mediated by CB1 receptor activation, as previously reported (Fontaine et al., 2020). Additionally, physostigmine (10 µM), an acetylcholinesterase inhibitor, was perfused for 15 min to evaluate endogenous 2-AG production in the MPP – DG synapse, as previously demonstrated in acute hippocampal slices (Wang et al., 2018b, 2018a). Finally, in another subset of experiments, JZL 184 (1 µM), an irreversible inhibitor of monoacylglycerol lipase (MAGL) that increases the 2-AG levels (Wang et al., 2016) was perfused for 15 min on MK-801-treated slices to examine the effects of MAGL inhibition during the delivery of LFS at 3 Hz.